Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R). Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons
The most prominent biochemical changes in PD involve the reduction of striatal dopamine levels, which may result in abnormal motor behaviour, including resting tremors, rigidity, and bradykinesia [1]
In the substantia nigra of PD patients and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD, key enzymes involved in reactive oxygen species (ROS) production, such as microglia NAPDH oxidase, are upregulated in damaged areas and contribute to DA neuronal cell death [6]
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. The primary neurodegeneration trigger remains uncertain; several pathophysiological mechanisms have been implicated, including ageing, highly dense microglia in the substantia nigra (SN), inflammation, oxidative/nitrosative stress, abnormal protein deposits, and decreased neurotrophic factors [4]. These mechanisms lead to microglia activation, which, in turn, favours an oxidative and inflammatory environment that is facilitative of neuronal death [5]. In vivo studies have shown that pharmacological activation of the CB2R can reduce the activation of microglia cells and inhibit dopaminergic cell death in the substantia nigra in PD models [14]. The influence of BCP on PD has not yet been explored
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